A56 THE ROLE OF THE STERILE ALPHA MOTIF (SAM) POINTED DOMAIN ETS FAMILY TRANSCRIPTION FACTOR (SPDEF) ON GOBLET CELL BIOLOGY AND INTESTINAL MUCUS PRODUCTION IN THE CONTEXT OF PARASITIC HOST DEFENSE.
Bibliographic record
Abstract
Abstract Background The intestinal mucus layer in the gastrointestinal (GI) tract acts as a physical protective barrier against luminal contents and potential invaders. Goblet cells, a specialized subset of intestinal epithelial cells, play a large role in synthesizing and secreting mucins, which are the structural building blocks of the intestinal mucus layer. The terminal differentiation and maturation of these goblet cells are regulated by sterile alpha motif (SAM) pointed domain ETS family transcription factor (SPDEF). Goblet cell biology and the intestinal mucus barrier is one of the most effective host response mechanisms against enteric parasitic infections, including Trichuris muris. However, no study has evaluated the relationship between SPDEF, goblet cell biology, and mucus production in the context of parasitic host defense. Aims To identify the relationship between SPDEF, goblet cell biology, and mucus production during T. muris infection and how this contributes to parasitic host defence. Methods For infection experiments, BALB/c mice were gavaged with ~300 T. muris eggs in 200 µl autoclaved distilled water. To explore the role of SPDEF in goblet cell and mucin responses during T. muris infection, SPDEF-/- and SPDEF+/+ mice were administered ~300 T. muris eggs and were sacrificed at days 14 and 21 post-infection (p.i) along with uninfected controls. Periodic Acid Schiff (PAS) staining was used to quantify goblet cells and immunofluorescence was used to identify Muc2+ and SPDEF+ cells. Enzyme-linked immunosorbent assays were used to evaluate Th2 cytokines, and qPCR was used to evaluate Muc2 and SPDEF expression. Results BALB/c mice infected with T. muris displayed increased SPDEF expression. On days 14 and 21 p.i., SPDEF-/- mice harboured significantly more worms than their SPDEF+/+ counterparts. These mice also displayed diminished levels of IL-4 and IL-13 at day 14 p.i. as well as decreased PAS+ and MUC2+ goblet cell numbers. Compared to SPDEF+/+ mice, on day 21 p.i., IL-4 was increased in infected SPDEF-/- mice, whereas levels of PAS+ and MUC2+ goblet cells retained a similar pattern to that of day 14 p.i. Interestingly, the number of PAS+ goblet cells, MUC2+ cells and Muc2 expression significantly increased after infection in SPDEF+/+ mice at day 14 and day 21 p.i. Conclusions Together, these results suggest that SPDEF is an important regulator of goblet cell function and mucus production during T. muris infection, ultimately contributing to parasitic host defense. Funding Agencies:
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".